Significant advances in molecular methods over the past 20 years have led to increasing knowledge of the genetic events associated with diseases of hematopoietic cells. Current knowledge of the exact molecular mutations causing several congenital and hereditary blood disorders have led to the availability of pre-natal diagnosis. In addition, continuing advances in the application of gene transfer technology make permanent correction of some diseases possible in the near future. A long term goal in many cases is the replacement of defective gene sequences in situ by homologous recombination technology so that the introduced and functional gene is inserted in a safe fashion and is appropriately regulated. The accomplishment of this long term goal requires an interdisciplinary approach to specific diseases by molecular and cell biologists, geneticists, and clinicians. The goal of a large group of scientists at Indiana University School of Medicine is to exploit recent advances in the understanding of the molecular defects of blood diseases, recent advances in the identification and purification of hematopoietic stem cells as well as the evolving use of alternative sources of stem cells and use of gene transfer and homologous recombination technology to bring about safe and permanent cures for several severe and devastating diseases of the blood. The proposed exploratory grant will provide support for the Center grant planning process which will occur over the next year.